Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Fungal Genet Biol. 2009 Dec;46(12):919-26. doi: 10.1016/j.fgb.2009.08.004. Epub 2009 Aug 15.
Paracoccidioides brasiliensis is characterized by a multiple budding phenotype and a polymorphic cell growth, leading to the formation of cells with extreme variations in shape and size. Since Cdc42 is a pivotal molecule in establishing and maintaining polarized growth for diverse cell types, as well as during pathogenesis of certain fungi, we evaluated its role during cell growth and virulence of the yeast-form of P. brasiliensis. We used antisense technology to knock-down PbCDC42's expression in P. brasiliensis yeast cells, promoting a decrease in cell size and more homogenous cell growth, altering the typical polymorphism of wild-type cells. Reduced expression levels also lead to increased phagocytosis and decreased virulence in a mouse model of infection. We provide genetic evidences underlying Pbcdc42p as an important protein during host-pathogen interaction and the relevance of the polymorphic nature and cell size in the pathogenesis of P. brasiliensis.
巴西副球孢子菌的特征是多芽生表型和多态细胞生长，导致形成形状和大小极端变化的细胞。由于 Cdc42 是建立和维持多种细胞类型极化生长的关键分子，以及在某些真菌的发病机制中，我们评估了其在细胞生长和巴西副球孢子菌酵母形式毒力中的作用。我们使用反义技术敲低 P. brasiliensis 酵母细胞中 PbCDC42 的表达，导致细胞大小减小和更均匀的细胞生长，改变了野生型细胞的典型多态性。表达水平降低还导致在感染的小鼠模型中吞噬作用增加和毒力降低。我们提供了宿主-病原体相互作用中 Pbcdc42p 作为重要蛋白的遗传证据，以及巴西副球孢子菌发病机制中多态性和细胞大小的相关性。
